a study of arry-371797 in patients with lmna-related dilated cardiomyopathy

Conditions: LMNA-Related Dilated Cardiomyopathy

Summary: this is a phase 2 pilot study, involving a 48-week treatment period, designed to test the effectiveness of investigational study drug arry-371797 in treating patients with symptomatic genetic dilated cardiomyopathy due to a lamin a/c gene mutation, and to further evaluate the drug's safety. approximately 12 patients from the us will be enrolled in this study.


Eligibility criteria:
key inclusion criteria: * patients with idiopathic dilated cardiomyopathy and stable new york heart association (nyha) class ii - iiia congestive heart failure (chf). * stable, guidelines-based medical and device therapy, without any chf hospitalizations or change in heart failure drug dose with ≥ 50% reduction in dose or ≥ 100% increase in dose in the past 3 months. * left ventricular (lv) end diastolic diameter by trans-thoracic echocardiography of \> 3.3 cm/m2 (for females) or 3.4 cm/m2 (for males) and/or lv ejection fraction ≤ 45%. * gene positive for a pathogenic mutation in the lmna gene, as determined by a clia-certified clinical laboratory (mutations including but not limited to: splice-site, non-sense, deletion mutations, a mis-sense mutation in a highly conserved codon, a mis-sense mutation involving a major charge change, a mis-sense mutation previously associated with genetic dilated cardiomyopathy). * within 3 weeks prior to first dose of study drug, completed distance during six minute walk test of ≥ 100 m and ≤ 350 m and/or ≥ 100 m and ≤ 450 m and ≤ 60% predicted distance and patient is symptomatic for dilated cardiomyopathy per investigator judgment. * on the day before and day of first dose of study drug, completed distance during six minute walk test of ≥ 100 m and ≤ 400 m (with the greater value within 10% of the lesser value) and/or ≥ 100 m and ≤ 475 m (with the greater value within 10% of the lesser value) and patient is symptomatic for dilated cardiomyopathy per investigator judgment. * acceptable hematology, hepatic and renal function laboratory values within 3 weeks prior to first dose of study drug. * additional criteria exist. key exclusion criteria: * unstable clinical cardiac symptoms requiring unscheduled hospitalization within 60 days prior to study start. * clinically significant coronary artery disease, as per investigator judgment. * currently receiving continuous intravenous (iv) inotrope infusion, or presence of a ventricular assist device, or history of prior heart transplantation. * any of the following within 60 days prior to study start: myocardial infarction, cardiac surgical procedures, acute coronary syndrome, hemodynamically destabilizing cardiac arrhythmia, serious systemic infection with evidence of septicemia, any major surgical procedure requiring general anesthesia. * uncorrected, hemodynamically significant primary valvular disease. * initiation of cardiac resynchronization therapy within 180 days prior to study start. * likelihood, in the investigator's opinion, of undergoing cardiac transplantation, left ventricular assist device or other device implantation, or other cardiac surgery within the next 6 months; or of requiring continuous iv inotropic treatment, or referral for hospice or end-of-life treatment. * active malignancy (except surgically-curative basal cell carcinoma, squamous cell carcinoma, or cervical carcinoma). * receiving chronic immunosuppressant therapy. * known positive serology for the human immunodeficiency virus (hiv), active hepatitis b and/or hepatitis c. * participation in any other investigational study of drugs or devices within 30 days prior to study start. * additional criteria exist.

Keywords: laminopathy